Gynecologic neoplasms can be among the most sensitive to hormonal manipulations. Studies of sex-steroid receptors in endometrial carcinomas have yielded important biologic and clinical observations, including a relationship between estrogen and progesterone receptor content concordance and tumor differentiation as well as enhanced predictive value for prognosis and response to hormone therapy. A limiting factor in the accurate evaluation of the hormonal receptor content of these gynecologic tumors has been the observation of high levels of receptor in normal myometrium and in tumor stromal elements. Such components frequently constitute a significant portion of the sample and cannot be mechanically dissected out efficiently. This difficulty is not experienced in breast tumors since the contribution to receptor content in this tissue is uniformly low, reflecting the very low levels of binding observed in normal breast epithelium and stroma. The development of highly specific and sensitive monoclonal antibodies to human estrogen receptor in conjunction with a verified immunohistochemical technique for receptor localization allows histologic dissection of the various components that contribute to the observed total receptor content as determined quantatively by biochemical assay. Using this monoclonal antibody to estrogen receptor (H222GammaSp) we propose to examine the immunohistochemical localization of receptor in over 500 gynecologic tumors that have been fresh frozen and stored at -80 degrees C since 1976 with clinical follow-up through this period, in order to compare the pattern and distribution of receptor to: 1) tumor differentiation and distribution of cytologic patterns, 2) quantitative ER and PgR, 3) possible contributions of non-tumor stromal elements to quantitative levels and 4) Prognosis and relative sensitivity and specificity of immunohistologic assay accounting for contributions of the various tissue elements in predicing clinical outcome and response to therapy. The immunohistochemical technique will be tested on cytologic aspirates and curettings which will greatly enhance its potential usefulness. Continued efforts towards the development of PgR monoclonal antibodies should permit the extension of the observations on immunohistochemical ER localizations.